EXPRESSION OF MATRIX METALLOPROTEINASES AND TIMPS IN HUMAN ABDOMINAL AORTIC-ANEURYSMS

Degradation of extracellular matrix, especially elastin, within the ao rtic wall is a hallmark of abdominal aortic aneurysms (AAAs). Normal t urnover of matrix proteins is mediated by a family of enzymes called m atrix metalloproteinases (MMPs). MMP activity is regulated by proteins called tissue inhibitors of metalloproteinases (TIMPs). We analyzed t he expression of all known MMPs with established elastolytic activity and TIMPs in human AAA and control tissue. mRNA coding for MMP-9, MMP- 2, human macrophage metalloelastase, MMP-7, TIMP-1, and TIMP-2 were am plified by reverse transcriptase-PCR in control and AAA tissue. A Nort hern blot assay was used to measure the levels of mRNA coding for MMP- 2, MMP-9, TIMP-1, and TIMP-2. Control aortic tissue was obtained from patients with occlusive disease and from organ donors. The expression of MMP-7 and human macrophage metalloelastase was not detected in any aortic specimens. By Northern blot analysis the mean level of MMP-2 mR NA was not significantly different between control groups and AAAs (no rmalized values: occlusive, 1.5 +/- 0.8, n = 3; donor, 4.5 +/- 2.2, n = 6; AAA, 4.0 +/- 0.95, n = 15). There was a significant increase in t he level of MMP-9 mRNA in AAA specimens (occlusive, 16.8 +/- 3, n = 3; donor, 5.7 +/- 1.2, n = 6; AAA, 56.7 +/- 11, n = 15, p = 0.0069). The levels of mRNA coding for TIMP-1 were not significantly different. Th ere was a small but statistically significant increase in TIMP-2 mRNA in AAA tissue. These data support the hypothesis that increased activi ty of MMP-9, but not MMP-2, is an important factor in the etiology of AAAs. This enhanced MMP-9 activity could then result in degradation of the ECM, leading to aneurysmal dilatation.